Physicochemical, ADMET and Druggable properties of Myricetin: A Key Flavonoid in Syzygium cumini that regulates metabolic inflammations
Abstract
Syzygium cumini (Myrtaceae) is a potential medicinal plant traditionally used in indigenous systems of medicines practiced in India and elsewhere due to its functional properties against metabolic inflammations viz., anti-hyperglycemic, anti-inflammatory, cardio-protective, and antioxidant activities. Targeting metabolic inflammation has emerged as a standalone strategy to attenuate metabolic disease. Myricetin (3,5,7,3′,4′,5′-hexahydroxyflavone) is one of the flavonoids from stem bark, leaf, flowers, fruits, pulp and seeds of S. cumini. Therefore, attention has been paid to explore bioactive potentials of this compound in S. cumini owing to its exemplary therapeutic prospective and health-promoting effects. Antioxidant effect of Myricetin from S. cumini has been though experimentally demonstrated, therapeutic potential of Myricetin has not been fully explored. In the present study, physicochemical, ADMET and druggability properties of Myricetin - a key flavonoid compound in S. cumini have been evaluated. Data implicates that this molecule of GRAS standard can be a novel jumble-sale lead in drug discovery.
Keywords: Plant Based Natural Products (PBNPs); Drug Discovery; Pharmacological Activity; ADMET Properties; Flavonoid; Myricetin; Syzygium cumini
Keywords:
Plant Based Natural Products (PBNPs), Drug Discovery, Pharmacological Activity, ADMET Properties, Flavonoid, Myricetin, Syzygium cuminiDOI
https://doi.org/10.22270/jddt.v11i4.4890References
Kong M, Xie K, Lv M, Li J, Yao J, Yan K, Wu X, Xu Y, Ye D. Anti-inflammatory phytochemicals for the treatment of diabetes and its complications: Lessons learned and future promise. Biomedicine & Pharmacotherapy. 2021; 133:110975. https://doi.org/10.1016/j.biopha.2020.110975
Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. Journal of natural products. 2007; 70(3):461-77. https://doi.org/10.1021/np068054v
Ahmed R, Tariq M, Hussain M, Andleeb A, Masoud MS, Ali I, Mraiche F, Hasan A. Phenolic contents-based assessment of therapeutic potential of Syzygium cumini leaves extract. PloS one 2019; 14(8):e0221318. https://doi.org/10.1371/journal.pone.0221318
Kumar S, Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. Scientific World Journal 2013; 162750 https://doi.org/10.1155/2013/162750
Middleton EJ Effect of plant flavonoids on immune and inflammatory cell function Advances in Experimental Medicine and Biology 1998; 439:175-182 https://doi.org/10.1007/978-1-4615-5335-9_13
Song X, Tan L, Wang M, Ren C, Guo C, Yang B, Ren Y, Cao Z, Li Y, Pei J (2021) Myricetin: A review of the most recent research. Biomedicine and Pharmacotherapy 134:111017. https://doi.org/10.1016/j.biopha.2020.111017
Perkin AG, Hummel JJ. LXXVI.-The coloring principle contained in the bark of Myrica nagi. Part I. Journal of the Chemical Society, Transactions. 1896; 69:1287-94 https://doi.org/10.1039/CT8966901287
Ong KC, Khoo HE Biological effects of Myricetin. General Pharmacology: The Vascular System 1997; 29(2):121-126. https://doi.org/10.1016/S0306-3623(96)00421-1
Jones JR, Lebar MD, Jinwal UK, Abisambra JF, Koren III J, Blair L, O'Leary JC, Davey Z, Trotter J, Johnson AG, Weeber E The diarylheptanoid (+)-a R, 11 S-myricanol and two flavones from bayberry (Myrica cerifera) destabilize the microtubule-associated protein Tau. Journal of natural products 2011; 74(1):38-44 https://doi.org/10.1021/np100572z
Ayyappan P, Ganesan K, Jayakumararaj R Ethnobotanic information on uncommon anti-diabetic medicinal plants from Alagarkoil forest reserve: Evidence based strategic rationale in management of diabetics. Int J Pharm Res 2019; 16:515-26
Umadevi I, Daniel M, Sabnis SD Chemotaxonomic studies on some members of Anacardiaceae Proceedings: Plant Sciences 1988; 98(3):205-208
Abd El-kader AM, El-Readi MZ, Ahmed AS, Nafady AM, Wink M, Ibraheim ZZ Polyphenols from aerial parts of Polygonum bellardii and their biological activities. Pharmaceutical Biology 2013; 51(8):1026-34 https://doi.org/10.3109/13880209.2013.775160
Chua LS, Latiff NA, Lee SY, Lee CT, Sarmidi MR, Aziz RA Flavonoids and phenolic acids from Labisia pumila (Kacip Fatimah). Food Chemistry 2011; 127(3):1186-1192. https://doi.org/10.1016/j.foodchem.2011.01.122
Lee KM, Kang NJ, Han JH, Lee KW, Lee HJ Myricetin down-regulates phorbol ester-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking activation of nuclear factor kappa B. Journal of Agricultural and Food Chemistry 2007; 55(23):9678-84. https://doi.org/10.1021/jf0717945
Semwal DK, Semwal RB, Combrinck S, Viljoen A Myricetin: A dietary molecule with diverse biological activities. Nutrients 2016; 8(2):90-97 https://doi.org/10.3390/nu8020090
Ong KC, Khoo HE Insulinomimetic effects of myricetin on lipogenesis and glucose transport in rat adipocytes but not glucose transporter translocation. Biochemical Pharmacology 1996; 51(4):423-9. https://doi.org/10.1016/0006-2952(95)02195-7
Li Y, Zheng X, Yi X, Liu C, Kong D, Zhang J, Gong M Myricetin: a potent approach for the treatment of type 2 diabetes as a natural class B GPCR agonist. FASEB J 2017; 31(6):2603-2611. https://doi.org/10.1096/fj.201601339R
Kwon O, Eck P, Chen S, Corpe CP, Lee JH, Kruhlak M, Levine M Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. The FASEB Journal 2007; 21(2):366-377. https://doi.org/10.1096/fj.06-6620com
Karunakaran U, Elumalai S, Moon JS, Jeon J-H, Kim ND, Park K-G, Won KC, Leem J, Lee I-K Myricetin protects against high glucose-induced β-cell apoptosis by attenuating endoplasmic reticulum stress via inactivation of cyclin-dependent kinase 5. Diabetes Metab J 2019; 43(2):192-205 https://doi.org/10.4093/dmj.2018.0052
Ramya S, Neethirajan K, Jayakumararaj R. Profile of bioactive compounds in Syzygium cumini-a review. J. Pharm. Res 2012; 5(8):4548-4553.
Aqil F, Gupta A, Munagala R, Jeyabalan J, Kausar H, Sharma RJ Antioxidant and antiproliferative activities of anthocyanin/ellagitannin-enriched extracts from Syzygium cumini L.(Jamun, the Indian Blackberry). Nutrition and Cancer 2012; 64(3):428-38. https://doi.org/10.1080/01635581.2012.657766
Gaspar RS, da Silva SA, Stapleton J, Fontelles JL, Sousa HR, Chagas VT, Alsufyani S, Trostchansky A, Gibbins JM, Paes AM. Myricetin, the main flavonoid in Syzygium cumini leaf, is a novel inhibitor of platelet thiol isomerases PDI and ERp5. Frontiers in Pharmacology. 2020; 10:1678. https://doi.org/10.3389/fphar.2019.01678
Zhou Y, Wu F, Li L, Shen X, Chen G, Wang X, Liang X, Tan M, Huang Z. Computational approaches in preclinical studies on drug discovery and development. Frontiers in Chemistry. 2020; 8:726-31. https://doi.org/10.3389/fchem.2020.00726
Park KS, Chong Y, Kim MK Myricetin: biological activity related to human health. Applied Biological Chemistry 2016; 59(2):259-69 https://doi.org/10.1007/s13765-016-0150-2
Holder S, Zemskova M, Zhang C, Tabrizizad M, Bremer R, Neidigh JW, Lilly MB, Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase. Mol Cancer Ther 2007; 6:163-172 https://doi.org/10.1158/1535-7163.MCT-06-0397
Phillips PA, Sangwan V, Borja-Cacho D, Dudeja V, Vickers SM, Saluja AK. Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Cancer Letters. 2011; 308(2):181-8. https://doi.org/10.1016/j.canlet.2011.05.002
Tsai SH, Liang YC, Lin‐Shiau SY, Lin JK. Suppression of TNFα‐mediated NFκb activity by myricetin and other flavonoids through downregulating the activity of IKK in ECV304 cells. Journal of Cellular Biochemistry. 1999; 74(4):606-15. https://doi.org/10.1002/(SICI)1097-4644(19990915)74:4<606::AID-JCB10>3.0.CO;2-W
Wang SJ, Tong Y, Lu S, Yang R, Liao X, Xu YF, Li X. Anti-inflammatory activity of myricetin isolated from Myrica rubra Sieb. et Zucc. leaves. Planta Medica. 2010; 76(14):1492-6. https://doi.org/10.1055/s-0030-1249780
Sato M, Murakami K, Uno M, Nakagawa Y, Katayama S, Akagi KI, Masuda Y, Takegoshi K, Irie K. Site-specific inhibitory mechanism for amyloid β42 aggregation by catechol-type flavonoids targeting the Lys residues. Journal of Biological Chemistry. 2013; 288(32):23212-24. https://doi.org/10.1074/jbc.M113.464222
Xu H, Ziegelin G, Schröder W, Frank J, Ayora S, Alonso JC, Lanka E, Saenger W. Flavones inhibit the hexameric replicative helicase RepA. Nucleic Acids Research. 2001; 29(24):5058-66. https://doi.org/10.1093/nar/29.24.5058
Pasetto S, Pardi V, Murata RM. Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model. PLoS One. 2014; 9(12):e115323. https://doi.org/10.1371/journal.pone.0115323
Li Y, Ding Y. Minireview: Therapeutic potential of myricetin in diabetes mellitus. Food Science and Human Wellness. 2012; 1(1):19-25. https://doi.org/10.1016/j.fshw.2012.08.002
Zamora-Ros R, Forouhi NG, Sharp SJ, Gonzalez CA, Buijsse B, Guevara M, van der Schouw YT, Amiano P, Boeing H, Bredsdorff L, Fagherazzi G. Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations. The Journal of Nutrition. 2014; 144(3):335-43. https://doi.org/10.3945/jn.113.184945
Furuno K, Akasako T, Sugihara N. The contribution of the pyrogallol moiety to the superoxide radical scavenging activity of flavonoids. Biological and Pharmaceutical Bulletin. 2002; 25(1):19-23. https://doi.org/10.1248/bpb.25.19
Gordon MH, Roedig-Penman A. Antioxidant activity of quercetin and myricetin in liposomes. Chemistry and Physics of Lipids. 1998; 97(1):79-85. https://doi.org/10.1016/S0009-3084(98)00098-X
Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006; 444(7121):860-7. https://doi.org/10.1038/nature05485
Cheng X, Siow RC, Mann GE. Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-Kelch-like ECH-associated protein 1 defense pathway. Antioxidants & Redox Signaling. 2011; 14(3):469-87. https://doi.org/10.1089/ars.2010.3283
Pandey KB, Mishra N, Rizvi SI. Myricetin may provide protection against oxidative stress in type 2 diabetic erythrocytes. Zeitschrift für Naturforschung C. 2009; 64(9-10):626-30. https://doi.org/10.1515/znc-2009-9-1004
Liu IM, Liou SS, Lan TW, Hsu FL, Cheng JT. Myricetin as the active principle of Abelmoschus moschatus to lower plasma glucose in streptozotocin-induced diabetic rats. Planta Medica. 2005l; 71(07):617-21. https://doi.org/10.1055/s-2005-871266
Tzeng TF, Liou SS, Liu IM. Myricetin ameliorates defective post-receptor insulin signaling via β-endorphin signaling in the skeletal muscles of fructose-fed rats. Evidence-Based Complementary and Alternative Medicine. 2011; 150752 https://doi.org/10.1093/ecam/neq017
Strobel P, Allard C, Perez-Acle T, Calderon R, Aldunate R, Leighton F. Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes. Biochemical Journal. 2005; 386(3):471-8. https://doi.org/10.1042/BJ20040703
Koren J, Jinwal UK, Jin Y, O'Leary J, Jones JR, Johnson AG, Blair LJ, Abisambra JF, Chang L, Miyata Y, Cheng AM. Facilitating Akt clearance via manipulation of Hsp70 activity and levels. Journal of Biological Chemistry. 2010; 285(4):2498-505. https://doi.org/10.1074/jbc.M109.057208
Chaturvedi A, Kumar MM, Bhawani G, Chaturvedi H, Kumar M, Goel RK. Effect of ethanolic extract of Eugenia jambolana seeds on gastric ulceration and secretion in rats. Indian Journal of Physiology and Pharmacology. 2007; 51(2):131.
Kumar A, Ilavarasan R, Deecaraman M, Aravindan P, Padmanabhan N, Krishan MR. Anti-diabetic activity of Syzygium cumini and its isolated compound against streptozotocin-induced diabetic rats. Journal of Medicinal Plants Research. 2013; 2(9):246-9.
Silva SD, Abreu IC, Silva GF, Ribeiro RM, Lopes AD, Cartágenes MD, Freire SM, Borges AC, Borges MO. The toxicity evaluation of Syzygium cumini leaves in rodents. Revista Brasileira de Farmacognosia. 2012; 22(1):102-8. https://doi.org/10.1590/S0102-695X2011005000181
Dang Y, Lin G, Xie Y, Duan J, Ma P, Li G, Ji G. Quantitative determination of myricetin in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry and its absolute bioavailability. Drug Research. 2014; 64(10):516-22. https://doi.org/10.1055/s-0033-1363220
Chagas VT, França LM, Malik S, Paes AM. Syzygium cumini (L.) skeels: a prominent source of bioactive molecules against cardiometabolic diseases. Frontiers in Pharmacology. 2015; 6:259. https://doi.org/10.3389/fphar.2015.00259
Subramanian SS, Nair AG. Myricetin and myricetin-3-Ol-rhamnoside from the leaves of Madhuca indica and Achras sapota. Phytochemistry. 1972; 7:247-256
Gordon A, Jungfer E, da Silva BA, Maia JG, Marx F. Phenolic constituents and antioxidant capacity of four underutilized fruits from the Amazon region. Journal of agricultural and Food Chemistry. 2011; 59(14):7688-99. https://doi.org/10.1021/jf201039r
Mahmoud II, Marzouk MS, Moharram FA, El-Gindi MR, Hassan AM. Acylated flavonol glycosides from Eugenia jambolana leaves. Phytochemistry. 2001; 58(8):1239-44. https://doi.org/10.1016/S0031-9422(01)00365-X
Bhatia IS, Bajaj KL. Chemical constituents of the seeds and bark of Syzygium cumini. Planta Medica. 1975; 28(08):346-52. https://doi.org/10.1055/s-0028-1097868
Published
Abstract Display: 1219
PDF Downloads: 1032
PDF Downloads: 122 How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).

.